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To fast or not to fast?

EAS/EFLM Consensus Statement offers new guidance for requirements for lipid testing

Plasma lipids are routinely measured in the fasting state. Yet clinicians recognise that there are practical issues, notably patient inconvenience especially among the elderly, children or those with diabetes, with the requirement for repeat visits if the individual is noncompliant. Furthermore, given that the postprandial state predominates during a 24-hour period, do fasting levels provide the best estimate of average daily plasma lipid and lipoprotein levels for cardiovascular risk assessment? Would it not be simpler for patients, laboratories and clinicians to measure plasma lipids in the nonfasting state, provided this approach is supported by the evidence?

This joint consensus statement from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has scrutinised the evidence and concluded that fasting is not routinely required for determination of a lipid profile.1 The document and an accompanying slide deck are now available from the EAS website http://www.eas-society.org/page/lipidprofile.

Does the use of nonfasting samples influence lipid levels?

Most but not all guidelines have recommended the use of fasting serum lipids largely based on the robustness of evidence from randomized controlled trials of lipid modifying therapy.2-4 While true, it should be acknowledged that there are also robust data for the use of nonfasting lipid measurement from population studies including more than 300,000 individuals, as well as clinical trials of statin therapy including more than 43,000 patients.

Importantly, there is the perception that the use of nonfasting samples may overestimate plasma triglycerides, perhaps pertinent in areas where consumption of a fast-food high-fat diet is prevalent. The totality of evidence, however, shows that plasma lipids and lipoproteins change only modestly in response to habitual food intake.5,6 Indeed, comparison of lipids measured in fasting versus nonfasting samples, showed only minor changes (increases in plasma triglycerides and decreases in total and low-density lipoprotein (LDL) cholesterol) which were transient and not clinically significant (as reported in the EAS/EFLM statement)1.

A potential issue was raised by data from a study showing a transient decrease in LDL cholesterol (by 0.6 mmol/L or 23 mg/dl) at 1-3 hours after eating in diabetes patients, which may be of possible clinical relevance when considering the need for lipid modifying therapy.5 However, as reduction in LDL cholesterol evident in subjects with and without diabetes was not statistically significant after adjusting for plasma albumin concentration (a marker of fluid intake), it was suggested that the decrement in LDL cholesterol observed may relate to haemodilution; this would also occur with fasting lipid profile testing, given that water is usually allowed ad libutum.7,8 Indeed, updated analyses including over 92,000 individuals in the Danish general population showed that at 1-6 hours, there were maximal mean increases in triglycerides of 0.3 mmol/l (26 mg/dl) and in remnant cholesterol of 0.2 mmol/l (8 mg/dl), and total, LDL and non-high-density lipoprotein (HDL) cholesterol each showed mean maximal decreases of 0.2 mmol/l (8 mg/dl), which were consistent with previous reports, and considered not clinically relevant. There was no change in lipoprotein(a), HDL cholesterol or apolipoprotein A-I.1

Does the use of nonfasting lipids influence cardiovascular risk assessment?

A key consideration for clinicians is whether the use of nonfasting lipids impacts cardiovascular risk prediction. In the most comprehensive meta-analysis to date from the Emerging Risk Factors Collaboration including more than 300,000 individuals,9 there was no indication that the use of nonfasting samples (in 20 trials) reduced the strength of the association between plasma lipids and lipoprotein levels and cardiovascular risk. On the contrary, nonfasting HDL cholesterol and nonfasting calculated LDL cholesterol were shown to be superior to corresponding fasting measures for cardiovascular risk prediction. These data are consistent with findings from other cohorts, such as Copenhagen General Population Study including more than 92,000 men and women, which confirmed significant associations for the risk of ischaemic heart disease and myocardial infarction for the highest versus lowest quintiles of nonfasting lipids, lipoproteins and apoliproteins (unpublished data).1

Collective evidence shows that fasting is not routinely required for assessing the plasma lipid profile.

Are there clinical settings where fasting lipid levels should be preferentially used?

The EAS/EFLM consensus suggests that fasting and nonfasting measurements of the lipid profile should be considered as complementary and not mutually exclusive (Table 1). For example, while fasting may be less important for initial screening, it may have particular value in diagnosis and assessment, such as establishing clinical diagnosis of genetically determined dyslipidaemia, or in obtaining baseline levels before initiation of lipid modifying therapy. Additionally, if nonfasting triglycerides are >5 mmol/L (440 mg/dl), a repeat lipid profile in the fasted state is recommended.

Table 1. When to use nonfasting versus fasting blood sampling to measure plasma lipids

Nonfasting sampling may be preferred
Fasting sampling may be required
  • Initial lipid screening
  • Cardiovascular risk assessment
  • Patients admitted with acute coronary syndrome*
  • Children • Diabetic patients**
  • Elderly patients
  • On stable drug therapy
  • If preferred by the patient
  • Nonfasting triglycerides >5 mmol/l (440 mg/dl)
  • Known hypertriglyceridaemia under management
  • Recovery from hypertriglyceridaemic pancreatitis
  • Initiation of therapy that can cause severe hypertriglyceridaemia
  • Additional fasting tests are required (e.g fasting glucose or therapeutic drug monitoring)

* Repeated lipid testing will be needed as acute coronary syndrome lowers lipids

** Diabetic hypertriglyceridaemia may be masked by fasting

The EAS/EFLM consensus initiative has made recommendations for flagging of nonfasting abnormal values, based on desirable cutpoints (Table 2). However, the EAS/EFLM emphasizes that life-threatening or extremely abnormal concentrations should trigger immediate referral to the lipid clinic or a clinician with an interest in lipids (Table 3).

Table 2. Desirable cutpoints for abnormal lipid levels

Parameter Nonfasting cutpoint for abnormal values
Fasting cutpoint for abnormal values
mmol/L mg/dl mmolL mg/dl
Triglycerides ≥2 ≥175 ≥1.7 ≥150
Total cholesterol ≥5 ≥190 ≥5 ≥190
LDL cholesterol ≥3 ≥115 ≥3 ≥115
Non-HDL cholesterol ≥3.9 ≥150 ≥3.8 ≥145
Remnant cholesterol ≥0.9 ≥35 ≥0.8 ≥30
Apolipoprotein B - ≥100 - ≥100
Lipoprotein(a) - ≥50 - ≥50
HDL cholesterol ≤1 ≤40 ≤1 ≤40
Apolipoprotein A1 - ≤125 - ≤125

Table 3. Extremely abnormal nonfasting levels for direct referral

Parameter
Value mmol/l (mg/dl)*
Suspected condition
Triglycerides
>10 (>880)
Chylomicronaemia syndrome with high risk of pancreatitis
LDL cholesterol (adult)
>13 (>500)
Homozygous familial hypercholesterolaemia
  >5 (>190) Heterozygous familial hypercholesterolaemia  
LDL cholesterol (children)  >4 (>155) Heterozygous familial hypercholesterolaemia  
Lipoprotein(a)  (>155)
(>99th percentile)
Very high cardiovascular risk for myocardial infarction or aortic valve stenosis

LDL cholesterol

Apolipoprotein B 
<0.3
(<10)
Genetic abetalipoproteinaemia 
HDL cholesterol
Apolipoprotein A1 
<0.2
(<10)
Genetic hypoalphaproteinaemia 

In conclusion, this EAS/EFLM consensus initiative provides an important resource for clinicians and laboratory personnel regarding the value of nonfasting measurement of the lipid profile. Such an approach offers a number of practical advantages, particularly in the setting of point-of-care assessment. Based on review of the evidence, nonfasting lipid testing is recommended for most individuals, and offers advantages especially for children, the elderly and those with diabetes.

References

1. Nordestgaard BG, Langsted A, Mora S, Kolovou G, Baum H, Bruckert E, Watts GF, Sypniewska G, Wiklund O, Borén J, Chapman MJ, Cobbaert C, Descamps OS, von Eckardstein A, Kamstrup PR, Pulkki K, Kronenberg F, Remaley AT, Rifai N, Ros E, Langlois M; European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) joint consensus initiative. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J 2016 Apr 26. pii: ehw152. [Epub ahead of print].
2. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
3. National Institute for Health and Clinical Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. NICE guidelines [CG181] Published July 2014; updated January 2015. https://www.nice.org.uk/guidance/CG181
4. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818/
5. Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation 2008;118:2047-56.
6. Mora S, Rifai N, Buring JE, Ridker PM. Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation 2008;118:993-1001.
7. Lund SS, Jensen T. Using nonfasting lipids- hemodilution or convenience? Clin Chem 2011;57:1336-8.
8. Simundic AM, Cornes M, Grankvist K, Lippi G, Nybo M. Standardization of collection requirements for fasting samples: for the Working Group on Preanalytical Phase (WG-PA) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). Clin Chim Acta 2014;432:33-7.
9. Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009;302:1993-2000.


 

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